EP4482545B1 - Verfahren zur produktion von gewebekonstrukten - Google Patents

Verfahren zur produktion von gewebekonstrukten

Info

Publication number
EP4482545B1
EP4482545B1 EP23706870.5A EP23706870A EP4482545B1 EP 4482545 B1 EP4482545 B1 EP 4482545B1 EP 23706870 A EP23706870 A EP 23706870A EP 4482545 B1 EP4482545 B1 EP 4482545B1
Authority
EP
European Patent Office
Prior art keywords
tissue
sample
blood
graft
construct
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
EP23706870.5A
Other languages
English (en)
French (fr)
Other versions
EP4482545C0 (de
EP4482545A1 (de
Inventor
Dobrila NESIC
Nicola DI MARZIO
Marc Thurner
Tiziano SERRA
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Mimix Biotherapeutics Sa
Original Assignee
Mimix Biotherapeutics Sa
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Mimix Biotherapeutics Sa filed Critical Mimix Biotherapeutics Sa
Publication of EP4482545A1 publication Critical patent/EP4482545A1/de
Application granted granted Critical
Publication of EP4482545C0 publication Critical patent/EP4482545C0/de
Publication of EP4482545B1 publication Critical patent/EP4482545B1/de
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5082—Supracellular entities, e.g. tissue, organisms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A61L27/362—Skin, e.g. dermal papillae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3683—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
    • A61L27/3695—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment characterised by the function or physical properties of the final product, where no specific conditions are defined to achieve this
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/60—Materials for use in artificial skin
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N13/00—Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0625—Epidermal cells, skin cells; Cells of the oral mucosa
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0697—Artificial constructs associating cells of different lineages, e.g. tissue equivalents
    • C12N5/0698—Skin equivalents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/40—Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2502/00—Coculture with; Conditioned medium produced by
    • C12N2502/11—Coculture with; Conditioned medium produced by blood or immune system cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2521/00—Culture process characterised by the use of hydrostatic pressure, flow or shear forces
    • C12N2521/10—Sound, e.g. ultrasounds
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2533/00—Supports or coatings for cell culture, characterised by material
    • C12N2533/30—Synthetic polymers
    • C12N2533/40—Polyhydroxyacids, e.g. polymers of glycolic or lactic acid (PGA, PLA, PLGA); Bioresorbable polymers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2533/00—Supports or coatings for cell culture, characterised by material
    • C12N2533/90—Substrates of biological origin, e.g. extracellular matrix, decellularised tissue
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/24—Immunology or allergic disorders
    • G01N2800/245—Transplantation related diseases, e.g. graft versus host disease

Definitions

  • the technology is versatile and perfectly suited for generating organized cell and particulate entity assemblies and for tissue engineering constructs.
  • US9688962 discloses a method of inducing spatial organization of cells in an in vitro culture system using ultrasound technology. This document teaches the use of this method for three-dimensional in vitro extracellular matrix remodelling and neovascularisation using a polymerised biological support structure as a scaffold.
  • WO2006097707 concerns a method for modulating the tensile strength and/or elastic strength of suspension of living cells by ultrasound stimulation, as well as a composition comprising such living cells having modulated tensile strength and/or elastic strength.
  • the invention is directed to skin equivalents.
  • US20140274802 concerns an engineered, three-dimensional liver tissue construct and a method or producing the construct using bio-inks.
  • the invention does not use SIM for producing the three-dimensional liver tissue constructs.
  • This invention aims to provide of a method to produce tissue constructs, which may for example be used as tissue grafts, such as skin grafts, that overcomes the shortcomings and limitations of the state of the art.
  • tissue constructs such as tissue grafts.
  • a rapid fabrication of a graft makes the method suitable for provision of required tissue grafts in emergency situations.
  • the invention should provide for the production of a point-of-care tissue graft.
  • the graft should be safe for the patient and effectively support internal or external wound healing.
  • the expansion should be increased, such as to allow for the production of tissue grafts with a significantly larger surface area than conventionally used methods.
  • the large tissue graft should be ready for application in a relatively short amount of time.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biotechnology (AREA)
  • Wood Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Cell Biology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Urology & Nephrology (AREA)
  • General Engineering & Computer Science (AREA)
  • Hematology (AREA)
  • Botany (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Physics & Mathematics (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Pathology (AREA)
  • Analytical Chemistry (AREA)
  • Toxicology (AREA)
  • Physics & Mathematics (AREA)
  • Food Science & Technology (AREA)
  • Composite Materials (AREA)
  • Materials Engineering (AREA)
  • Developmental Biology & Embryology (AREA)

Claims (16)

  1. Ein Verfahren zur Herstellung eines menschlichen oder tierischen Gewebekonstrukts, umfassend
    - Bereitstellen einer Gewebeprobe oder einer Vielzahl von Mikrogeweben,
    - Bereitstellen eines Volumens einer flüssigen Probe zum Suspendieren der Gewebeprobe,
    - Suspendieren oder Resuspendieren der Gewebeprobe oder der Mikrogewebe in dem Volumen der flüssigen Probe in einem Behälter, wobei der Behälter einen vorzugsweise flachen Boden aufweist,
    - Aussetzen des Behälters, der die Gewebeprobe oder die in der flüssigen Probe suspendierten Mikrogewebe enthält, einem statischen akustischen Wellenfeld, um zu bewirken, dass sich Aggregate von Zellen, die in der Gewebeprobe enthalten sind, oder Aggregate der Mikrogewebe in einem durch die statischen akustischen Wellen definierten Muster anordnen,
    dadurch gekennzeichnet, dass
    - die flüssige Probe eine Blutprobe ist, wie eine Vollblutprobe oder eine verarbeitete Blutprobe, wobei die verarbeitete Blutprobe gerinnungsfördernde Komponenten enthält oder mit solchen ergänzt ist, um die Gerinnung der flüssigen Probe zu bewirken, und
    - dass das Verfahren den Schritt der Koagulation der Blutprobe umfasst, um eine koagulierte Blutschicht zu bilden, die ein Gerüst für die freie Migration der Aggregate bereitstellt, um beispielsweise ein gemustertes Blutgewebekonstrukt zu erzeugen.
  2. Verfahren nach Anspruch 1, das ferner einen Inkubationsschritt bei Temperaturen im Bereich von 20°C bis 40°C, idealerweise bei 35°C bis 38°C, ex vivo oder in vitro umfasst, um das Zellwachstum und/oder die Reifung des gemusterten Blutgewebekonstrukts zu erleichtern.
  3. Verfahren nach Anspruch 1 oder 2, wobei das akustische Wellenfeld eine Frequenz von 10 Hz bis 600 Hz, vorzugsweise von 30 Hz bis 200 Hz, oder von 50 Hz bis 100 Hz aufweist.
  4. Verfahren nach einem der Ansprüche 1 bis 3, wobei die Einwirkungszeit der Felder im Bereich von 1 Minute bis 20 Minuten, vorzugsweise von 2 Minuten bis 10 Minuten liegt.
  5. Verfahren nach einem der Ansprüche 1 bis 4, wobei es sich bei den Mikrogeweben um Organoide, Sphäroide oder Kombinationen davon handelt.
  6. Verfahren nach einem der Ansprüche 1 bis 4, wobei es sich bei den Mikrogeweben um Mikrografts handelt.
  7. Verfahren nach Anspruch 6, wobei die Mikrotransplantate eine maximale transversale Abmessung von nicht mehr als 1000 µm, oder nicht mehr als 500 µm, vorzugsweise von nicht mehr als 100 µm, beispielsweise 80 µm ± 20 µm, aufweisen.
  8. Verfahren nach einem der Ansprüche 1 bis 4, wobei es sich bei der Gewebeprobe um eine Suspension von Zellen, gegebenenfalls von konzentrierten Zellen, handelt, die beispielsweise aus Fettgewebe, Lymphgewebe, Knochenmark oder Blut stammen.
  9. Verfahren nach einem der Ansprüche 1 bis 8, wobei mehrere Iterationen des Verfahrens durchgeführt werden, um eine Reihe von gemusterten Blutgewebekonstrukten zu erzeugen, die anschließend als Schichten übereinandergelegt werden.
  10. Verfahren nach Anspruch 9, wobei eine oder mehrere Schichten jeweils unterschiedliche Arten von Gewebeproben oder Mikrogeweben umfassen.
  11. Verfahren nach Anspruch 9 oder 10, wobei sich zwei oder mehr Schichten in der Art der Gewebeprobe und/oder des Mikrogewebes, die in diesen Schichten enthalten sind, voneinander unterscheiden.
  12. Verfahren nach einem der Ansprüche 1 bis 11 zur Herstellung von Gewebetransplantaten, z. B. Hauttransplantaten, ferner umfassend das Übertragen des gemusterten Blutgewebekonstrukts auf eine vliesartigen Trägerstruktur, z. B. auf eine Silikonträgerfolie.
  13. Verwendung nach einem der Ansprüche 1 bis 11 hergestellten Gewebekonstrukts für in vitro oder ex vivo diagnostische Zwecke.
  14. Diagnoseverfahren, das mit einem nach einem der Ansprüche 1 bis 11 hergestellten Gewebekonstrukt durchgeführt wird, umfassend die folgenden Schritte
    - Aussetzen des Gewebekonstrukts einem Reagens zur Identifizierung einer biologischen Einheit, beispielsweise eines Biomarkers, oder zur Identifizierung eines Analyten von Interesse,
    - Nachweis des Vorhandenseins, der Abwesenheit oder des Gehalts der biologischen Einheit oder des Analyten im Gewebekonstrukt, und
    - Vergleichen des erhaltenen Nachweisergebnisses mit dem erwarteten Vorhandensein, der Abwesenheit oder dem Gehalt der biologischen Einheit oder des Analyten in gesundem Gewebe.
  15. Das Verfahren nach Anspruch 14 weiters umfassend das Diagnostizieren einer Krankheit oder eines Krankheitsstatus auf der Grundlage des Vergleichsschritts.
  16. Eine Bank von biologischen Gewebetransplantaten, die nach einem der Ansprüche 1 bis 12 hergestellt wurde.
EP23706870.5A 2022-02-22 2023-02-16 Verfahren zur produktion von gewebekonstrukten Active EP4482545B1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP22158003.8A EP4230233A1 (de) 2022-02-22 2022-02-22 Verfahren zur produktion von gewebekonstrukten
PCT/IB2023/051401 WO2023161769A1 (en) 2022-02-22 2023-02-16 Method for producing tissue constructs

Publications (3)

Publication Number Publication Date
EP4482545A1 EP4482545A1 (de) 2025-01-01
EP4482545C0 EP4482545C0 (de) 2025-12-17
EP4482545B1 true EP4482545B1 (de) 2025-12-17

Family

ID=80446774

Family Applications (2)

Application Number Title Priority Date Filing Date
EP22158003.8A Withdrawn EP4230233A1 (de) 2022-02-22 2022-02-22 Verfahren zur produktion von gewebekonstrukten
EP23706870.5A Active EP4482545B1 (de) 2022-02-22 2023-02-16 Verfahren zur produktion von gewebekonstrukten

Family Applications Before (1)

Application Number Title Priority Date Filing Date
EP22158003.8A Withdrawn EP4230233A1 (de) 2022-02-22 2022-02-22 Verfahren zur produktion von gewebekonstrukten

Country Status (6)

Country Link
US (1) US20250164466A1 (de)
EP (2) EP4230233A1 (de)
CN (1) CN118742340A (de)
AU (1) AU2023226495A1 (de)
CA (1) CA3251554A1 (de)
WO (1) WO2023161769A1 (de)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4624564A1 (de) * 2024-03-28 2025-10-01 mimiX Biotherapeutics SA Vorrichtung zur erzeugung einer verfestigten gewebeprobe

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0505203D0 (en) * 2005-03-14 2005-04-20 Intercytex Ltd Skin composition treatment
EP2432421A4 (de) 2009-05-19 2013-03-06 Univ Rochester Ultraschalltechnologie zur steuerung der räumlichen organisation von zellen und proteinen in gezüchteten geweben
SG10201607331WA (en) * 2011-09-30 2016-11-29 Somalogic Inc Cardiovascular risk event prediction and uses thereof
US9442105B2 (en) * 2013-03-15 2016-09-13 Organovo, Inc. Engineered liver tissues, arrays thereof, and methods of making the same
JP6901404B2 (ja) * 2015-01-21 2021-07-14 ユタ バレー ユニバーシティ 空間的な収束、操作、およびパターニングのための定在波場の高調波変調用システムおよび方法
EP4061923A4 (de) 2019-11-22 2024-01-03 Cutiss AG Verfahren und systeme zum produzieren von hauttransplantaten

Also Published As

Publication number Publication date
EP4482545C0 (de) 2025-12-17
CN118742340A (zh) 2024-10-01
EP4482545A1 (de) 2025-01-01
CA3251554A1 (en) 2023-08-31
US20250164466A1 (en) 2025-05-22
AU2023226495A1 (en) 2024-08-22
EP4230233A1 (de) 2023-08-23
WO2023161769A1 (en) 2023-08-31

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